Subtribe Angraecinae (Orchidaceae: Vandeae) are mainly distributed in Africa, but with two genera, Campylocentrum and Dendrophylax, restricted to the Neotropics. As a widespread Neotropical genus, Campylocentrum constitutes an appropriate model for revealing biogeographical patterns in this area and investigating routes of colonization and dispersal. In this study, we reconstructed phylogenetic relationships of the genus with Bayesian inference and maximum parsimony analyses of combined nuclear (ITS rDNA and Xdh) and plastid (matK exon, rpl32-trnL spacer, trnL intron, trnL-trnF spacer and ycf1 exon) DNA datasets, aimed at establishing a new infrageneric classification for this taxonomically complex genus. Based on the most comprehensive phylogenetic tree, we investigated the biogeographical history of Campylocentrum by estimating divergence times, inferred using fossil and secondary calibrations applying a relaxed-clock model approach, and reconstructing ancestral areas of distribution under a time-stratified likelihood model. The phylogenetic analyses provided strong support for the majority of the clades. Campylocentrum is monophyletic, and we recognize five sections based upon strongly supported clades. We conclude that the African angraecoid ancestor of Campylocentrum and Dendrophylax dispersed to the Antilles. Campylocentrum is estimated to be a relatively young genus (late Miocene, c. 8.2 Mya) and its most recent common ancestor had a disjunct distribution in the Antilles and Parana dominion. During the Pliocene, the five sections diverged and expanded their distributions in the Neotropics, and in the Pleistocene diversification was experienced by some of the Terminal clades. We hypothesize that the evolutionary history of Campylocentrum was strongly influenced by orogenic events during the Pliocene and climatic fluctuations during the Pleistocene.